[Causes, diagnosis, and treatment of anemia in the elderly].
Healthy elderly people are mildly anemic peripheral blood data on 3,583 healthy elderly people (1,590 men and 1,993 women aged 65 years or older) from among those undergoing medical examinations at our hospital in the 8 years from 1988 to 1995 were compiled into 5-year age groups. For both men and women the mean values of red blood cell count, hemoglobin, and hematocrit were slightly lower among older subjects. The main causes of this apparent reduction may be a decrease in the number of hematopoietic stem cells and regression of the hematopoietic microenvironment. Observation of arteries in specimens of hematopoietic bone marrow obtained from the spines of elderly people showed arteriosclerotic changes such as greater hypertrophy of the media than of the intima, and adventitial fibrous hypertrophy. The number of venous sinuses was low and the amount of adipose tissue was high compared to the bone marrow of younger people. The cell density and the ratio of hematopoietic tissue to fat tended to be lower in older subjects. The number of erythroid burst-forming units formed after 14 days in culture medium containing erythropoietin was 28 +/- 19 in 32 healthy elderly people, which was significantly lower than the number in 30 young people 54 +/- 30, (p < 0.005). The value for erythroid colony-forming units was 170 +/- 67 in eight healthy people, which was much lower than in young people, 276 +/- 54. In the elderly subjects, the plasma iron disappearance time (PIDT/2) was 60-80 min (mean: 71.9 min), which was similar to that in the young, but the percent red cell iron utilization was 67.6%-84.9% (mean: 79.7%), which was slightly lower than in younger people. When the diagnostic criterion for anemia in the elderly was set at a hemoglobin value of 11.0 g/ dl, about 13% of outpatients who came to our Geriatrics department were found to have anemia, and in most of them the anemia had resulted from another disease. In conclusion, anemia in the elderly is likely to be affected by reduction in the function of various organs and by the decreased reserves associated with aging. The causes of anemia are complex and diagnosis is often difficult. The present article gives a general outline of the diagnosis and treatment of common types of primary and secondary anemia in the elderly.


Therapeutic Approaches to Inherited Optic Neuropathies.
As a group, inherited optic neuropathies represent an important cause of severe irreversible visual loss among children and young adults. Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common forms encountered in clinical practice and several shared disease pathways have emerged that contribute to retinal ganglion cell loss, and eventually visual failure. In this review, the author critically appraises the evidence base for the various therapeutic strategies that have been put forward to treat these two mitochondrially determined optic neuropathies, including future developments. Innovative in vitro fertilization techniques to prevent female carriers of childbearing age from transmitting pathogenic mitochondrial DNA mutations to their biological children will also be discussed.


The post-synaptic scaffolding protein tamalin regulates ligand-mediated trafficking of metabotropic glutamate receptors.
Group I metabotropic glutamate receptors (mGluRs) play important roles in various neuronal functions and have also been implicated in multiple neuropsychiatric disorders like fragile X syndrome, autism, and others. mGluR trafficking not only plays important roles in controlling the spatiotemporal localization of these receptors in the cell but also regulates the activity of these receptors. Despite this obvious significance, the cellular machineries that control the trafficking of group I metabotropic glutamate receptors in the central nervous system have not been studied in detail. The post-synaptic scaffolding protein tamalin has been shown to interact with group I mGluRs and also with many other proteins involved in protein trafficking in neurons. Using a molecular replacement approach in mouse hippocampal neurons, we show here that tamalin plays a critical role in the ligand-dependent internalization of mGluR1 and mGluR5, members of the group I mGluR family. Specifically, knockdown of endogenous tamalin inhibited the ligand-dependent internalization of these two receptors. Both N-terminal and C-terminal regions of tamalin played critical roles in mGluR1 endocytosis. Furthermore, we found that tamalin regulates mGluR1 internalization by interacting with S-SCAM, a protein that has been implicated in vesicular trafficking. Finally, we demonstrate that tamalin plays a critical role in mGluR-mediated internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, a process believed to be the cellular correlate for mGluR-dependent synaptic plasticity. Taken together, these findings reveal a mechanistic role of tamalin in the trafficking of group I mGluRs and suggest its physiological implications in the brain.


The Wnt receptor Ryk is a negative regulator of mammalian dendrite morphogenesis.
The unique dendritic architecture of a given neuronal subtype determines its synaptic connectivity and ability to integrate into functional neuronal networks. It is now clear that abnormal dendritic structure is associated with neuropsychiatric and neurodegenerative disorders. Currently, however, the nature of the extrinsic factors that limit dendritic growth and branching within predetermined boundaries in the mammalian brain is poorly understood. Here we identify the Wnt receptor Ryk as a novel negative regulator of dendritic arborisation. We demonstrate that loss of Ryk in mouse hippocampal and cortical neurons promotes excessive dendrite growth and branching in vitro. Conversely, overexpression of wildtype Ryk restricts these processes, confirming that Ryk acts to restrain dendrite arborisation. Furthermore, we identify a hitherto uncharacterized membrane proximal subdomain crucial for Ryk-mediated suppression of dendrite morphogenesis, suggesting that it may act through a novel signalling pathway to constrain dendrite complexity. We also demonstrate that Ryk performs a similar function in vivo as Ryk haploinsufficient postnatal animals exhibit excessive dendrite growth and branching in layer 2/3 pyramidal neurons of the somatosensory cortex. These findings reveal an essential role for Ryk in regulating dendrite complexity and raise the intriguing possibility that it may influence neural plasticity by modifying dendritic structure.


Role of long-range correlations in the quenching of spectroscopic factors.
We consider the proton and neutron quasiparticle orbits around the closed-shell (56)Ni and (48)Ca isotopes. It is found that large model spaces (beyond the capability of shell model applications) are necessary for predicting the quenching of spectroscopic factors. The particle-vibration coupling is identified as the principal mechanism. Additional correlations--due to configuration with several particle-hole excitations--are estimated using shell model calculations and generate an extra reduction which is < or approximately equal to 4% for most quasiparticle states. The theoretical calculations nicely agree with (e, e'p) and inverse kinematics knockout experiments. These results open a new path for a microscopic understanding of the shell model.


Identifying Health Information Technology Needs of Oncologists to Facilitate the Adoption of Genomic Medicine: Recommendations From the 2016 American Society of Clinical Oncology Omics and Precision Oncology Workshop.
At the ASCO Data Standards and Interoperability Summit held in May 2016, it was unanimously decided that four areas of current oncology clinical practice have serious, unmet health information technology needs. The following areas of need were identified: 1) omics and precision oncology, 2) advancing interoperability, 3) patient engagement, and 4) value-based oncology. To begin to address these issues, ASCO convened two complementary workshops: the Omics and Precision Oncology Workshop in October 2016 and the Advancing Interoperability Workshop in December 2016. A common goal was to address the complexity, enormity, and rapidly changing nature of genomic information, which existing electronic health records are ill equipped to manage. The subject matter experts invited to the Omics and Precision Oncology Workgroup were tasked with the responsibility of determining a specific, limited need that could be addressed by a software application (app) in the short-term future, using currently available genomic knowledge bases. Hence, the scope of this workshop was to determine the basic functionality of one app that could serve as a test case for app development. The goal of the second workshop, described separately, was to identify the specifications for such an app. This approach was chosen both to facilitate the development of a useful app and to help ASCO and oncologists better understand the mechanics, difficulties, and gaps in genomic clinical decision support tool development. In this article, we discuss the key challenges and recommendations identified by the workshop participants. Our hope is to narrow the gap between the practicing oncologist and ongoing national efforts to provide precision oncology and value-based care to cancer patients.


To Have and to Hold: Selection for Seed and Fruit Retention During Crop Domestication.
Crop domestication provides a useful model system to characterize the molecular and developmental bases of morphological variation in plants. Among the most universal changes resulting from selection during crop domestication is the loss of seed and fruit dispersal mechanisms, which greatly facilitates harvesting efficiency. In this review, we consider the molecular genetic and developmental bases of the loss of seed shattering and fruit dispersal in six major crop plant families, three of which are primarily associated with seed crops (Poaceae, Brassicaceae, Fabaceae) and three of which are associated with fleshy-fruited crops (Solanaceae, Rosaceae, Rutaceae). We find that the developmental basis of the loss of seed/fruit dispersal is conserved in a number of independently domesticated crops, indicating the widespread occurrence of developmentally convergent evolution in response to human selection. With regard to the molecular genetic approaches used to characterize the basis of this trait, traditional biparental quantitative trait loci mapping remains the most commonly used strategy; however, recent advances in next-generation sequencing technologies are now providing new avenues to map and characterize loss of shattering/dispersal alleles. We anticipate that continued application of these approaches, together with candidate gene analyses informed by known shattering candidate genes from other crops, will lead to a rapid expansion of our understanding of this critical domestication trait.


Seasonal variation in the prevalence of preeclampsia.
Hypertension in pregnancy is one of the three factors of maternal mortality. Etiology of the disease is unknown, but the many factors contributing to the identification and control of it can be taken a step to prevent and reduce the symptoms of the disease. The purpose of this study was to determine the prevalence of preeclampsia (high-blood pressure) in different seasons of the year. The present retrospective cross-sectional study was conducted on more than 8,000 pregnant women visiting Assali specialized hospital from 2011 to 2013. Required data was collected through questionnaire checklist. The Chi-square test with multiple comparisons was used to compare the frequencies of pregnancy-induced hypertension (PIH) according to the month of year, and adjustment of multiplicity was conducted using Bonferroni's method. Student's t-test was used to compare the means of PIH prevalence rates. In all analyses, P < 0.05 was taken to indicate statistical significance. In these 8000 woman admitted to labor, overall prevalence of PIH was 3.8 ± 0.6%. The prevalence rate of PIH was highest in the summer (4.5%) and lowest frequent in the winter (2.7%), respectively. In July, the prevalence rate was significantly higher than those for any other month (4.7%), and in March, it was lower prevalence than for any month (2.2%), respectively. Using the Chi-square test, a significant difference between the incidence of disease was observed in summer and winter (P < 0.001). The prevalence rate of PIH was higher for delivery in summer and early spring and lowest for winter delivery among Khorramabad women based on these results; it seems that changes in temperature and humidity in different seasons can affect preeclampsia, and preeclampsia increases with increasing frequency temperature.


Quantitative analysis of rabeprazole sodium in commercial dosage forms by spectrophotometry.
The main aim of this work is to develop and validate two spectrophotometric methods for the quantitative analysis of rabeprazole sodium in commercial dosage forms. Method A is based on the reaction of drug with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in the presence of ammonium cerium(IV) nitrate in acetic acid medium at room temperature to form red-brown product which absorbs maximally at 470 nm. Method B utilizes the reaction of rabeprazole sodium with 1-chloro-2,4-dinitrobenzene (CDNB) in dimethyl sulfoxide (DMSO) at 45+/-1 degrees C to form yellow colored Meisenheimer complex. The colored complex has a characteristic band peaking at 420 nm. Under the optimized reaction conditions, proposed methods are validated as per ICH guidelines. Beer's law is obeyed in the concentration ranges of 14-140 and 7.5-165 microg ml(-1) with linear regression equations of A=6.041 x 10(-4)+1.07 x 10(-2)C and A=1.020 x 10(-3)+5.0 x 10(-3)C for methods A and B, respectively. The limits of detection for methods A and B are 1.38 and 0.75 microg ml(-1), respectively. Both methods have been applied successfully for the estimation of rabeprazole sodium in commercial dosage forms. The results are compared with the reference UV spectrophotometric method.


Partially irreversible cold-induced lipid phase transitions in mammalian sperm plasma membrane domains: freeze-fracture study.
In an effort to investigate the nature of the cellular injury caused when mammalian spermatozoa are cooled prior to cryopreservation, the occurrence of thermal phase transitions amongs the lipid components of the sperm plasma membrane was investigated by the use of freeze-fracture electron microscopy. The mechanisms by which glycerol and egg yolk exert protective effects during semen cooling and freezing were also examined. Ram and blackbuck spermatozoa, maintained at 30 degrees C prior to fixation at this temperature, exhibited randomly distributed intramembranous particles over the acrosomal, postacrosomal, and flagellar regions of the plasma membrane. In contrast, spermatozoa fixed at 5 degrees C after slow cooling to this temperature exhibited particle clustering over the postacrosomal region of the head as well as over the tail. These effects were not influenced by the presence of egg yolk or glycerol during the cooling procedure, although these substances protected the spermatozoa against loss of motility. Particle clustering over the sperm tail, induced by the slow cooling process, was found to be only partially reversible. The extensive areas of particle-free lipid, noted to result from the cooling procedure, were absent if the spermatozoa were rewarmed to 30 degrees C; however, the original distribution of particles was not restored and numerous small particle-free domains persisted. It is proposed that this type of irreversible change within the sperm plasma membrane may contribute to the loss of motility and fertility suffered by spermatozoa after cooling and freezing. Furthermore, it is suggested that protective substances such as egg yolk may exert their effects by countering these deleterious changes, rather than by preventing their occurrence.


[Microsurgical treatment of adult craniopharyngiomas in 156 cases].
To explore the clinical features, surgical approaches and outcomes of craniopharyngioma in adults. A total of 156 cases of adult craniopharyngioma underwent microsurgery at our hospital were retrospectively reviewed and classified into four types according to the location of tumor relative to sellar diaphragm and the third ventricle. They were divided into four groups: intrasellar type (n = 6), suprasellar & extraventricular type (n = 59), intraventricular type (n = 63) and mixed type (n = 28). Unilateral subfrontal approach was chosen in 9 cases, anterior interhemispheric approach in 14 cases, pterional approach in 102 cases, transcallosal approach in 28 cases and transsphenoidal approach in 3 cases. Tumors were totally removed in 124 cases (79.5%), subtotally removed in 25 cases (16%) and partially removed in 7 cases (4.5%). Two patients died after surgery. Pituitary stalk was identified and protected intraoperatively in 69 cases, and postoperative diabetes insipidus occurred in 109 cases. The follow-up period ranged from 3 months to 5 years. 75.3% of the cases were capable of normal work and life and tumor recurred in 26 cases. Selection of appropriate approach is the key to successful microsurgery for craniopharyngioma according to the site and growth pattern of tumor.


[Electroconvulsive therapy in depressed adolescents].
Two patients, young women aged 15 and 17, both suffering from major depression with psychotic features, were resistant to treatment with antidepressive regimen and psychotherapy. Both patients became severely suicidal and were subsequently successfully treated with electroconvulsive therapy (ECT). The second patient needed maintenance ECT once a month in order to stay in remission. Whereas ECT is a well-studied and accepted treatment option in adult psychiatry, in child psychiatry people are reluctant to even consider this option. This resistance is partly based on the possible side effects ofECT i.e. memory problems. As a result, the effect ofECT in adolescents has not yet been well studied. In 2004, the American Academy of Child and Adolescent Psychiatry proposed guidelines for the use of ECT in adolescents. Following these guidelines, the use ofECT in adolescents seems to be a safe treatment option, however further research to the effect of ECT in this age group is warranted.


Cloning and site-directed mutagenesis of human ADP-ribosylarginine hydrolase.
Mono-ADP-ribosylation of arginine is a reversible modification of proteins with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyzing the opposing reactions in the cycle. ADP-ribosylarginine hydrolases differ in their dithiothreitol (DTT) requirements. Rat and mouse hydrolases require DTT for maximal activity, but calf, guinea pig, and human hydrolases are DTT-independent. To define the molecular basis for these differences, brain ADP-ribosylarginine hydrolases were cloned. Deduced amino acid sequences of mouse and rat hydrolases were 94% identical with 5 conserved cysteines. The human hydrolase sequence was 83% identical to that of rat but contained only 4 cysteines with cysteine 108 in rat corresponding to serine 103 in human. To investigate the role of rat cysteine 108, human and rat wild-type hydrolases and mutants, in which serine 103 in human was replaced by cysteine (S103C) and cysteine 108 in rat was replaced by serine (C108S), were expressed in Escherichia coli. Affinity-purified anti-rat brain hydrolase antibodies reacted with recombinant wild-type rat hydrolase, but only weakly with the C108S mutant. They did not react with human wild-type or the S103C mutant. Human hydrolase and rat C108S were DTT-independent; human S103C was, however, DTT-dependent. These data clearly show that cysteine 108 in rat hydrolase plays a critical role in DTT dependence and may be important in immunoreactivity.


Single stranded DNA-guided electropolymerization of polythionine nanostrip to the sensing of H(2)O(2).
The electropolymerization of thionine with the guidance of DNA molecular template was described in this paper. The prepared polythionine (PTH) dispersed uniformly on the electrode surface and presented a novel flexual nanostrip morphology with the average diameter of 90nm and length of 500nm. However, PTH fabricated without DNA-guided electropolymerization presented a clustered granular morphology. The electrochemical redox behavior of PTH via DNA-guided electropolymerization was considerably enhanced compared to that of PTH without DNA molecular template. The significant improvement of the redox property might be attributed to the in situ PTH chains growth along DNA strands. In neutral environment, the PTH/DNA on the carbon paste electrode showed a pair of well-defined redox peaks and excellent electrocatalytic activity toward the reduction of H(2)O(2). Under optimal conditions, H(2)O(2) was amperometrically determined by using the as-prepared PTH/DNA nanostrips in the concentration range of 0.99-8.26mM.


Partial molecular characterization of an antigenic structure associated to cells of common acute lymphocytic leukaemia (ALL).
A heteroantiserum against common human acute lymphocytic leukaemia (ALL) cells was raised in rabbits. This antiserum was rendered specific for common ALL cells by extensive absorption with different human tissue. A specific antigen associated to common ALL cells was solubilized by sodium deoxycholate from ALL plasma membranes and identified by indirect immunofluorescence. By analytical chromatography, two antigenically active peaks were found. The apparent molecular weights were calculated to be 55,000 and 110,000.


A CPRS subscale to assess mental symptoms in workers exposed to jet fuel--some methodological considerations.
A CPRS subscale was constructed for the assessment of mental symptoms in 30 workers exposed to jet fuel and in 30 matched non-exposed controls. All subjects were interviewed in random order by the same psychiatrist. Interviews were recorded on tapes later used for evaluation of rating-rerating and inter-rater reliability, which were in the range of rs 0.75--0.85. The average score of the exposed group exceeded significantly that of the control group. Items concerned with symptoms referred to as neurasthenic and as neurotic differentiated best between the groups. It appears that the subscale is sensitive enough differentiate between two groups of non-patient individuals and has helped establishing that occupational exposure to jet fuel may induce a psycho-organic reaction.


The melanoma epidemic: res ipsa loquitur.
Many have debated whether or not we are in the midst of a melanoma epidemic. Some facts are clear and helpful to this debate, while others are less clear. The incidence and mortality of melanoma have increased over the last several decades, but the incidence has risen faster than the mortality. The incidence has risen 3%-7% on average over several decades and even more rapidly among Caucasian men and the elderly. In the U.S., the incidence in men is higher than in women after the age of 40, and the difference between men and women increases from age 40 until the end of life. The incidence in the U.S. has risen most rapidly among in situ and localized lesions, but distant and regional disease have increased as well. Among localized disease, in the U.S. from 1988-1997, all stages increased by comparable amounts. This strongly argues against the idea that the increase in incidence of melanoma is only due to early detection of thin lesions or biologically benign lesions, at least during the time period studied. On the other hand, early detection of thin lesions may well account for lower increases in mortality than incidence and improvements in survival. Survival has increased from approximately 60% in the 1960s to 89% in recent years. Improvements in survival appear to be related to earlier diagnosis, rather than an improvement in survival of a given stage. Studies consistently point to a major role for UV light exposure as the most important risk factor for those individuals with a phenotypic susceptibility. Public health efforts aim at primary and secondary prevention strategies. Primary prevention strategies attempt to prevent people from developing melanoma, primarily through avoiding exposure to UV light. There is a particular emphasis on avoidance of UV light exposure in childhood and young adulthood, when it appears the risk is greatest. When strict avoidance cannot be adhered to, sunscreens have been logically recommended. Secondary prevention strategies include screening campaigns and educational campaigns. Many of these strategies appear promising but require further rigorous testing. The melanoma epidemic has arisen for a variety of reasons including: a true increase in melanomas of malignant behavior, a particularly high increase in localized and in situ lesions, and an increase in the number of biopsies performed, which may have resulted in an increased detection of less aggressive lesions. The contribution of possible changes in the diagnostic criteria for melanoma to the increased incidence remains unknown.


Comparison of standing balance between female collegiate dancers and soccer players.
This study was designed as a comparison study of two cohorts. The hypothesis of this study was that soccer players and dancers have different balance abilities and that these differences could be objectively measured using center of pressure measurements. Center of pressure (COP) measurements are reproducible and have been validated in the literature for assessing standing balance. The literature does not provide sensitive enough techniques for discriminating between two groups of athletes with excellent standing balance. A Matscan pressure mat (Tekscan, Boston, MA) was used to compare COP change variability between 32 female collegiate soccer players and 32 dancers. COP was used to calculate sway index, center acquisition time, sway path length and sway velocity as measures of standing balance. The dancers had significantly better balance scores (p<0.05) in 5 of 20 balance tests. Results for the remaining 15 balance tests were not significantly different. These data show that standing balance characteristics of dancers and soccer players can be objectively measured using COP data. Dancers have certain standing balance abilities that are better than those of soccer players. The COP measurements in this study can be used as a tool in future studies investigating standing balance in different groups of athletes.


Mafenide acetate solution dressings: an adjunct in burn wound care.
A continuation of the study of 5% aqueous Sulfamylon solution dressings in burned patients was analyzed in 150 consecutive cases. The rate of invasive infection and mortality was not excessive. Dressings were used as an adjunct to other topical chemotherapeutic agents as well as homo/heterograft skin in the overall burn care program. Sulfamylon soaks were shown to be effective for debridement, granulation tissue protection and preparation, and bacterial control. The dressings were comfortable when in place and the wounds appeared clean. Epithelialization was not hampered so that the dressings could be utilized in partial thickness wounds as well as for mesh autografts on extensive burn surfaces=


Utility of glycated hemoglobin in diagnosing type 2 diabetes mellitus: a community-based study.
Although glycated hemoglobin (HbA1c) has recently been incorporated as a diagnostic test by the American Diabetes Association, its validity needs to be established in Asian Indians in a community setting. The objective of the study was to assess the validity of HbA1c as a screening and diagnostic test in individuals with newly detected diabetes mellitus. Community based randomized cross sectional study in urban Chandigarh, a city in north India, from April 2008 to August 2009. Subjects included 1972 subjects aged 20 yr or older. Intervention included an oral glucose tolerance test and glycated hemoglobin in all the subjects. Utility of HbA1c as a diagnostic method in newly detected diabetes mellitus subjects was evaluated. Using World Health Organization criteria for diagnosis of diabetes mellitus, 134 (6.7%) had newly detected diabetes mellitus, 192 (9.7%) known diabetes mellitus, 329 (16.6%) prediabetes, and 1317 (69.4%) were normal of 1972 people screened. Using only the ADA criteria, 38% people were underdiagnosed. An HbA1c level of 6.1% had an optimal sensitivity and specificity of 81% for diagnosing diabetes. A HbA1c level of 6.5% (+/-2 SD) and 7% (+/-2.7 SD) had sensitivity and specificity of 65 and 88% and 42 and 92%, respectively, with corresponding positive predictive value and negative predictive value of 75.2 and 96.5% and 90.4 and 94.4%, respectively, for diagnosis of newly detected diabetes mellitus. A HbA1c cut point of 6.1% has an optimal sensitivity and specificity of 81% and can be used as a screening test, and a cut point of 6.5% has optimal specificity of 88% for diagnosis of diabetes.


Long-lasting depression of soleus motoneurons excitability following repetitive magnetic stimuli of the spinal cord in multiple sclerosis patients.
The effect of repetitive magnetic stimulation at the spinal level on the soleus H-reflex amplitude was evaluated in II MS patients with lower limb spasticity and in nine healthy subjects. In MS patients stimulation with a train of 16 stimuli at 25 Hz induced a decrease in amplitude to 61.2 +/- 25.7% of the unconditioned H-reflex amplitude at interstimulus interval (ISI) of 10-1000 ms (P < 0.01). The amount of decrease in H-reflex amplitude was highly dependent on the stimulation intensity and the placement of the coil, and to a lesser extent influenced by the stimulation frequency. No decrease in motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation was seen following trains of 16 stimuli at mid-thoracic in contrast to the post-stimulation depression in H-reflex amplitude which could imply that mechanisms acting at presynaptic level were involved. In response to repetitive magnetic stimuli for 5 min, a long-lasting decrease in H-reflex amplitude to a level of about 70% of the pre-stimulation H-reflex amplitude occurred in MS patients (P < 0.01). A similar although not significant decrease was observed in healthy subjects. We propose that long-lasting depression of the soleus H-reflex amplitude after repetitive magnetic stimuli is due to long-term depression of the synaptic transmission.


Evolutionary and biogeographical implications of degraded LAGLIDADG endonuclease functionality and group I intron occurrence in stony corals (Scleractinia) and mushroom corals (Corallimorpharia).
Group I introns and homing endonuclease genes (HEGs) are mobile genetic elements, capable of invading target sequences in intron-less genomes. LAGLIDADG HEGs are the largest family of endonucleases, playing a key role in the mobility of group I introns in a process known as 'homing'. Group I introns and HEGs are rare in metazoans, and can be mainly found inserted in the COXI gene of some sponges and cnidarians, including stony corals (Scleractinia) and mushroom corals (Corallimorpharia). Vertical and horizontal intron transfer mechanisms have been proposed as explanations for intron occurrence in cnidarians. However, the central role of LAGLIDADG motifs in intron mobility mechanisms remains poorly understood. To resolve questions regarding the evolutionary origin and distribution of group I introns and HEGs in Scleractinia and Corallimorpharia, we examined intron/HEGs sequences within a comprehensive phylogenetic framework. Analyses of LAGLIDADG motif conservation showed a high degree of degradation in complex Scleractinia and Corallimorpharia. Moreover, the two motifs lack the respective acidic residues necessary for metal-ion binding and catalysis, potentially impairing horizontal intron mobility. In contrast, both motifs are highly conserved within robust Scleractinia, indicating a fully functional endonuclease capable of promoting horizontal intron transference. A higher rate of non-synonymous substitutions (Ka) detected in the HEGs of complex Scleractinia and Corallimorpharia suggests degradation of the HEG, whereas lower Ka rates in robust Scleractinia are consistent with a scenario of purifying selection. Molecular-clock analyses and ancestral inference of intron type indicated an earlier intron insertion in complex Scleractinia and Corallimorpharia in comparison to robust Scleractinia. These findings suggest that the lack of horizontal intron transfers in the former two groups is related to an age-dependent degradation of the endonuclease activity. Moreover, they also explain the peculiar geographical patterns of introns in stony and mushroom corals.


Octreotide treatment does not improve impaired glucose uptake in cirrhosis.
Forearm glucose uptake during a hyperglycaemic (10 mmol/l) glucose clamp was diminished to 33% of the normal value (p = 0.012) in six cirrhotic patients compared with matched control subjects. Fasting insulin concentrations were significantly elevated in the cirrhotic patients confirming insulin resistance which may have been induced by chronic hyperinsulinaemia. The cirrhotic patients received one week of treatment with 50 micrograms octreotide subcutaneously three times daily which reduced pre-dose fasting insulin levels from 26.2 +/- 7.9 to 18.1 +/- 6.2 mU/l p < 0.005, and post dose levels to 7.0 +/- 3.5 mU/l p < 0.005. However when the glucose clamp was repeated 20 hours after the last dose of octreotide no change was detected in clamp glucose requirements, forearm glucose uptake, or stimulated insulin secretion. It was concluded that one week of lowering insulin levels does not reverse the insulin resistance of cirrhosis.


Soy isoflavones avert chronic inflammation-induced bone loss and vascular disease.
Evidence from epidemiological, clinical and animal studies suggests a link may exist between low bone density and cardiovascular disease, with inflammatory mediators implicated in the pathophysiology of both conditions. This project examined whether supplementation with soy isoflavones (IF), shown to have anti-inflammatory properties, could prevent tissue expression of TNF-alpha and the development of skeletal pathology in an animal model of chronic inflammation. Eight-week old, intact, female C57BL/6J mice were used. In Phase 1, a lipopolysaccharide (LPS)-dose response study (0, 0.133, 1.33 and 13.3 mug/d) was conducted to determine the LPS dose to use in Phase 2. The results indicated the 1.33 mug LPS/d dose produced the greatest decrease in lymphocytes and increase in neutrophils. Subsequently, in Phase 2, mice were randomly assigned to one of six groups (n = 12-13 per group): 0 or 1.33 mug LPS/d (placebo or LPS) in combination with 0, 126 or 504 mg aglycone equivalents of soy IF/kg diet (Control, Low or High dose IF). Mice were fed IF beginning 2 wks prior to the 30-d LPS study period. At the end of the study, no differences were detected in final body weights or uterine weights. In terms of trabecular bone microarchitecture, muCT analyses of the distal femur metaphysis indicated that LPS significantly decreased trabecular bone volume (BV/TV) and number (TbN), and increased separation (TbSp). Trabecular bone strength (i.e. total force) and stiffness were also compromised in response to LPS. The High IF dose provided protection against these detrimental effects on microarchitecture, but not biomechanical properties. No alterations in trabecular thickness (TbTh), or cortical bone parameters were observed in response to the LPS or IF. Immunohistomchemical staining showed that tumor necrosis factor (TNF)-alpha was up-regulated by LPS in the endothelium of small myocardial arteries and arterioles as well as the tibial metaphysis and down-regulated by IF. These results suggest IF may attenuate the negative effects of chronic inflammation on bone and cardiovascular health. Additional research is warranted to examine the anti-inflammatory properties of the soy isoflavones and the mechanisms underlying their prevention of chronic inflammation-induced bone loss.


Delivery of hyperoside by using a soybean protein isolated-soy soluble polysaccharide nanocomplex: Fabrication, characterization, and in vitro release properties.
Nanoparticles made from natural proteins and polysaccharides are green, biodegradable, and sustainable. In this study, soybean protein isolate (SPI) and soybean soluble polysaccharide (SSPS) were employed as delivery vehicles for hyperoside (HYP) to explore the mechanism of the formation of complexes and evaluate the performance of this mechanism at different pH values. The structures of SPI-SSPS-HYP complexes were studied by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM), and the stability was evaluated based on free radical scavenging ability, loading rate, and simulated release. The results showed that nanoparticles were subjected to non-covalent electrostatic complexation, which was affected mainly by electrostatic, hydrogen bond, and hydrophobic interactions, and the optimal encapsulation efficiency was 85.56% at pH 3.5. Encapsulated HYP retained its high antioxidant capacity. This study provides a new strategy for developing a biodegradable nanocarrier with superior encapsulation properties, enhancing the application range of HYP.


Oral Health and Risk of Upper Gastrointestinal Cancers in a Large Prospective Study from a High-risk Region: Golestan Cohort Study.
Tooth loss and periodontal disease have been associated with several cancers, and poor oral health may be an important risk factor for upper gastrointestinal (UGI, i.e., esophageal and gastric) cancers. We assessed the relationship between oral health and UGI cancers using a large prospective study of over 50,000 adults living in Golestan Province, Iran, a high-incidence area for these cancers. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for the association between three different measures of oral health [frequency of tooth brushing; number of missing teeth; and the sum of decayed, missing, and filled teeth (DMFT)] and UGI cancers. During a median follow-up duration of 13 years, there were 794 incident UGI cancers (396 esophageal and 398 gastric cancers). Daily tooth brushing was associated with a decreased risk of developing both esophageal (HR = 0.670; 95% CI: 0.486-0.924) and gastric (HR = 0.741; 95% CI: 0.544-1.01) cancers (combined UGI cancer HR = 0.697; 95% CI: 0.558-0.871) compared with never brushing. Tooth loss in excess of the loess smoothed, age- and sex-specific median number of teeth lost was significantly associated with esophageal (HR = 1.64; 95% CI: 1.08-2.47) and gastric cancers (HR = 1.58; 95% CI: 1.05-2.38). There were some adverse associations between DMFT and UGI cancers but most were not statistically significant. These results suggest increased risk of developing UGI cancers among individuals with poor oral health, and those who do not perform regular oral hygiene. PREVENTION RELEVANCE: Poor oral health is associated with the risk of upper gastrointestinal cancers, and oral hygiene practices may help prevent these cancers.


Congenital terminal transverse deformity of upper limb: clinical and radiological findings in a sporadic care.
Congenital transverse limb anomalies are rare, which affect upper and/or lower limbs and may accompany several syndromic malformations. We present a sporadic male subject with congenital, unilateral transverse arrest of the left hand. The affected arm was observed to be short with reduced zeugopod and truncated palm. Fingers were represented by five bead-like nubbins. Roentgenographic examination revealed short radius and ulna with hypoplastic distal heads, absent carpals/metacarpals, and a hypoplastic bony island in each nubbin. Consanguinity was denied, and the subject had no symptoms in the orofacial, neurological and skeletal systems. Detailed clinical data with literature survey is presented.


High glucose enhances cAMP level and extracellular signal-regulated kinase phosphorylation in Chinese hamster ovary cell: Usage of Br-cAMP in foreign protein β-galactosidase expression.
Glucose is a carbon source for Chinese hamster ovary (CHO) cell growth, while low growth rate is considered to enhance the production of recombinant proteins. The present study reveals that glucose concentrations higher than 1 g/L reduce the growth rate and substantially increase in cAMP (∼300%) at a high glucose concentration (10 g/L). High glucose also enhances the phosphorylation of extracellular signal-regulated kinase (ERK) and p27kip by Western blot analysis. To determine whether the phosphorylation of ERK is involved in the mechanism, a cyclic-AMP dependent protein kinase A (PKA) inhibitor (H-8) or MEK (MAPKK) inhibitor (PD98059) was added to block ERK phosphorylation. We show that both the high glucose-induced ERK phosphorylation and growth rate return to baseline levels. These results suggest that the cAMP/PKA and MAP signaling pathways are involved in the abovementioned mechanism. Interestingly, the direct addition of 8-bromo-cAMP (Br-cAMP), a membrane-permeable cAMP analog, can mimic the similar effects produced by high glucose. Subsequently Br-cAMP could induce β-galactosidase (β-Gal) recombinant protein expression by 1.6-fold. Furthermore, Br-cAMP can additionally enhance the β-Gal production (from 2.8- to 4.5-fold) when CHO cells were stimulated with glycerol, thymidine, dimethyl sulfoxide, pentanoic acid, or sodium butyrate. Thus, Br-cAMP may be used as an alternative agent in promoting foreign protein expression for CHO cells.


Valproic acid and chromatin remodeling in schizophrenia and bipolar disorder: preliminary results from a clinical population.
Levels of acetylated Histone 3 and 4 proteins are strongly predictive of a chromatin structure that is conducive to gene expression. In cell and animal studies, valproic acid is a potent inhibitor of histone deactylating enzymes, and consequently results in increased levels of acetylated Histone 3 (acH3) and acetylated Histone 4 proteins (acH4). To examine this effect in a clinical setting, 14 schizophrenic and bipolar patients were treated with valproic acid (Depakote ER), either as monotherapy or in combination with antipsychotics, over a period of 4 weeks. AcH3 and acH4 levels from lymphocyte nuclear protein extracts were measured by Western Blot. Treatment with Depakote ER resulted in a significant increase of acH3 and a trend-level increase of acH4. Levels of valproic acid were positively and significantly correlated with percent increase in acH3 but not acH4. Schizophrenia patients were significantly less likely to increase their acH3 and acH4 levels after 4 weeks on Depakote ER. The authors consider these results in the context of future application of HDAC inhibitors to the treatment of psychiatric disorders.


The role of microglia in the progression of glaucomatous neurodegeneration- a review.
Glaucoma is a serious leading cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) does not always stop glaucomatous neurodegeneration and the optic nerve may continue to be damaged in the normal IOP. Microglial activity has been recognized to play essential roles in pathogenesis of the central nervous system (CNS) as well as retinal ganglion cell (RGC) survival. The relationship between the neurodegeneration and the microglia cells in glaucoma is very complicated and still remains unclear. In the present review, we summarize the recent studies of mechanisms of microglia in glaucoma neurodegeneration, which might provide new ways to treat glaucoma.


Carcass traits and the occurrence of dark cutters in pregnant and nonpregnant feedlot heifers.
The objective of this study was to determine whether the occurrence of dark cutters and selected carcass traits differ between pregnant and nonpregnant feedlot heifers. Feedlot heifers (n = 8,292) were identified at slaughter as being either nonpregnant, pregnant with a moderate-sized fetus (midgestation), or pregnant with a large fetus (late gestation). This was based on visual appraisal of a gravid uterus at the evisceration table. After chilling (24 to 72 h), carcass data were collected. Cattle originated from 23 different commercial feedyards located within a 350-km radius of a commercial slaughter facility located in southwest Kansas. Across slaughter lots, the incidence of pregnancy varied from 0 to 25% with an overall mean of 4.74%. Carcass traits of heifers with moderate or large fetuses did not differ (P > .15). Compared with carcasses from nonpregnant heifers, carcasses from pregnant heifers were 4.5 kg lighter (P < .01), had .11 cm more fat thickness (P < .01), and exceeded the number of carcasses that graded Choice or Prime by 6% (P < .01). Carcasses from pregnant heifers had higher maturity scores (P < .01) and there was no incidence of dark cutters (P < .01) compared with a 1.7% incidence of dark cutters in carcasses from nonpregnant heifers. Any economical advantage in the pregnant heifers due to their higher percentage of Choice carcasses and lower incidence of dark cutters may be offset by their increased carcass fat thickness and lower dressing percentage.


Predicting posttraumatic stress symptoms longitudinally in a representative sample of hospitalized injured adolescents.
Adolescents constitute a high-risk population for traumatic physical injury, yet few longitudinal investigations have assessed the development of posttraumatic stress disorder (PTSD) symptoms over time in representative samples. Between July 2002 and August 2003, 108 randomly selected injured adolescent patients ages 12 to 18 and their parents were interviewed at baseline and again 2, 5, and 12 months postinjury. Initially, participants were screened for PTSD symptoms with the PTSD Reaction Index (PTSD-RI) and depressive symptoms with the Center for Epidemiologic Studies Depression Scale, as well as preinjury trauma. Random-coefficient regression was used to assess the association between baseline clinical, injury, and demographic characteristics and the development and maintenance of PTSD symptoms longitudinally. Between 19% and 32% of adolescents screened positive for PTSD (i.e., had PTSD-RI scores of > or =38) during the course of the 12 months after the injury. Higher initial adolescent PTSD and depressive symptoms, higher emergency department heart rate, greater objective event severity, and greater parental preinjury trauma were significant independent predictors of higher adolescent PTSD symptoms. For a substantive minority of hospitalized adolescents, high PTSD symptom levels persist during the 12 months after injury. Clinical characteristics readily identifiable after the acute injury predict the development of PTSD symptoms over time. Real-world clinical trials that test screening and intervention procedures for representative samples of at-risk youths are warranted.


Fenofibrate Solid Dispersion Processed by Hot-Melt Extrusion: Elevated Bioavailability and Its Cell Transport Mechanism.
Fenofibrate (FNB) is an effective drug for the treatment of hypertriglyceridemia, hypercholesterolemia as well as mixed hyperlipidemia. However, due to its poor aqueous solubility, FNB has the problem of poor oral absorption followed by low bioavailability. The aim of this research was to construct FNB amorphous solid dispersion employing PVP VA64 as the carrier by hot-melt extrusion method, in order to improve the oral bioavailability. Additionally, the cell transport experiment was conducted to further investigate the mechanism of promoted osmotic absorption. The physical state of the obtained solid dispersion was characterized using SEM, DSC and XRD. Besides, in vitro Caco-2 cells were used to evaluate the cytotoxicity of the carrier and mimic gastrointestinal drug permeation. At last, in vitro dissolution test and in vivo bioavailability study were also carried out. The prepared FNB solid dispersion was found to be an amorphous state after hot-melt extrusion process. In vitro cytotoxicity test on Caco-2 cells confirmed the excellent biocompatibility of the carrier PVP VA64. Besides, transwell cell transport assay and in vitro dissolution test revealed that FNB released from amorphous solid dispersion was equipped with an improved transmembrane transport and dissolution rate. Moreover, pharmacokinetic study in beagle dogs showed that comparing with commercial micronized product Lipanthyl®, the oral bioavailability of FNB solid dispersion was significantly enhanced (2.45 fold). In conclusion, PVP VA64 can be regarded as a promising polymer to enhance the bioavailability of poorly water-soluble drugs such as FNB processed by hot-melt extrusion. Besides, investigations on the mechanism of the enhanced penetration are expected to lay a foundation on the subsequent development of effective and practical solid dispersion.


Aggregation of qualitative studies--From theory to practice: Patient priorities and family medicine/general practice evaluations.
Aggregation (i.e., meta-ethnography or meta-synthesis) of qualitative studies remains relatively rare and controversial. We have attempted this procedure within an investigation of patient priorities and evaluations of primary care in order to triangulate an instrument development process as well as explore associated dilemmas. The procedures included a literature search of qualitative research on patient priorities and evaluations and creation of a framework for quality assessment of retrieved papers. The tool for the evaluation of quality in qualitative studies was piloted, refined, and applied to the retrieved literature. The articles were equally distributed between two teams in random fashion, and inter-rater agreement calculated. Finally, we formulated and applied a strategy for aggregation of data from included papers that allowed comparison to a systematic review of quantitative studies on the topic. Thirty-seven articles met inclusion criteria. Twenty-four of these articles were of sufficient quality to be included in the qualitative aggregation. Inter-rater agreement ranged from 0.22 to 0.77 and 0.38 to 0.60 for pair and assessor comparisons, respectively. The aggregation strategy enabled synthesis within sub-categories of the heterogeneous papers. We have devised a modestly reliable instrument to assess the quality of qualitative work. The procedure for quality assessment and aggregation appears to be both feasible and potentially useful, though both theoretical and practical problems underline the need for further refinement prior to widespread utilization of this approach. An instrument to assess the quality of qualitative work within the context of aggregation efforts is described. Calculating inter-rater reliability in this framework can support future quality assessments. A method of breaking a heterogeneous collection of included papers into sub-categories to enable aggregation of qualitative studies is applied and demonstrates its feasibility and potential usefulness.


Non-Antidepressant Treatment of Generalized Anxiety Disorder.
Generalized anxiety disorder (GAD) is a prevalent and very disabling anxiety disorder. First-line medications are antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenalin reuptake inhibitors (SNRIs). However, a substantial number of patients do not reach remission while on antidepressants and they may develop troublesome side effects, which highlights the necessity of new therapeutic options for GAD. The purpose of this review is to discuss all non-antidepressant treatments studied in GAD. We searched MedLine for English articles published between 1980 and 2012, containing the following keywords: "generalized (or generalised) anxiety disorder" OR "anxiety disorder", AND "drug therapy" OR "herbal medicine". 76 articles were finally selected. Pregabalin is the anticonvulsant with the most robust level of evidence in GAD. It rapidly reduces anxiety, has a safe side effect profile and presents a low potential for abuse. Among antipsychotics, quetiapine is the one of choice in GAD, with similar efficacy to SSRIs in low dosages, yet with lower overall tolerability. Benzodiazepines, buspirone and hydroxyzine are Food and Drugs administration (FDA) approved for GAD and have relatively good evidence of efficacy. Other drugs (betablockers, zolpidem, riluzole, etc.) and natural remedies (e.g. Piper methysticum) could be potential treatment options, yet additional research is warranted. Pregabalin and quetiapine are the two most promising non-antidepressant treatments for GAD.


Study of the growth of capped ZnO nanocrystals: a route to rational synthesis.
We report the study of complex and unexpected dependencies of nanocrystal size as well as nanocrystal-size distribution on various reaction parameters in the synthesis of ZnO nanocrystals using poly(vinyl pyrollidone) (PVP) as a capping agent. This method establishes a qualitatively different growth mechanism to the anticipated Ostwald ripening behavior. The study of size-distribution kinetics and an understanding of the observed non-monotonic behaviors provides a route to rational synthesis. We used a simple, but accurate, approach to estimate the size-distribution function of nanocrystals from the UV-absorption spectrum. Our results demonstrate the accuracy and generality of this approach, and we also illustrate its application to various semiconducting nanocrystals, such as ZnO, ZnS, and CdSe, over a wide size range (1.8-5.3 nm).


Ileo-colic intussusception in premature neonate.
Intussusception in neonatal age is very rare. A 12-day-old child was referred from peripheral hospital with history of intolerance to feed, absolute constipation, abdominal distension and significant bilious aspirate. Per-rectal examination revealed necrotic haemorrhagic fluid. The patient was treated on the lines of necrotising enterocolitis in the referring hospital. On further investigation and exploration, the patient turned out to be ileo-colic intussusception which is exceedingly less common in premature neonates. Hence, other causes of intestinal obstruction should also be considered along with vigilant clinical outlook in neonates.


Management of Post-Viral Postural Orthostatic Tachycardia Syndrome With Craniosacral Therapy.
Postural Orthostatic Tachycardia Syndrome (POTS) is a rare disorder of the autonomic nervous system. The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed. This case report is about a patient with post-viral neuropathic POTS. Neuropathic POTS is believed to be due to the damage of small nerve fibers that regulate the constriction of the blood vessels in the limb and abdomen, which leads to interference with vasoconstriction, and therefore causes tachycardia. Current literature emphasizes a treatment that is based on lifestyle modifications, such as increasing water and salt intake, and symptomatic pharmacological treatment. In this case, the 39-year-old male ptient was treated with osteopathic manipulative treatment (OMT), specifically the compression of the fourth ventricle (CV4), which has been associated with the production of hyperparasympathetic and anti-inflammatory effects and, hence, helps overcome the small-fiber neuropathy caused by the viral illness. We found that the CV4 technique led to the successful remission of the patient's symptoms. Therefore, we propose craniosacral therapy as a successful single management modality in patients with POTS.


Acute effect of daily fine particulate matter pollution on cerebrovascular mortality in Shanghai, China: a population-based time series study.
Numerous studies have investigated the impacts of ambient fine particulate matter (PM2.5) on human health. In this study, we examined the association of daily PM2.5 concentrations with the number of deaths for the cerebrovascular disease on the same day, using the generalized additive model (GAM) controlling for temporal trend and meteorological variables. We used the data between 2012 and 2014 from Shanghai, China, where the adverse health effects of PM2.5 have been of particular concern. Three different approaches (principal component analysis, shrinkage smoothers, and the least absolute shrinkage and selection operator regularization) were used in GAM to handle multicollinear meteorological variables. Our results indicate that the average daily concentration of PM2.5 in Shanghai was high, 55 μg/m3, with an average daily death for cerebrovascular disease (CVD) of 62. There was 1.7% raised cerebrovascular disease deaths per 10 μg/m3 increase in PM2.5 concentration in the unadjusted model. However, PM2.5 concentration was no longer associated with CVD deaths after controlling for meteorological variables. The results were consistent in the three modelling techniques that we used. As a large number of people are exposed to air pollution, further investigation with longer time period including individual-level information is needed to examine the association.


Alterations in the default mode-salience network circuit provide a potential mechanism supporting negativity bias in depression.
Aberrant effective connectivity between default mode (DMN) and salience (SAL) networks may support the tendency of depressed individuals to find it difficult to disengage from self-focused, negatively-biased thinking and may contribute to the onset and maintenance of depression. Assessment of effective connectivity, which can statistically characterize the direction of influence between regions within neural circuits, may provide new insights into the nature of DMN-SAL connectivity disruptions in depression. Functional magnetic resonance imaging (fMRI) was collected from 38 individuals with a history of major depression and 50 healthy comparison participants during completion of an emotion-word Stroop task. Activation within DMN and SAL networks and effective connectivity between DMN and SAL, assessed via Granger causality, were examined. Individuals with a history of depression exhibited greater overall network activation, greater directed connectivity from DMN to SAL, and less directed connectivity from SAL to DMN than healthy comparison participants during negative-word trials. Among individuals with a history of depression, greater DMN-to-SAL connectivity was associated with lower overall network activation and worse task performance during positive-word trials; this pattern was not observed among healthy participants. Present findings indicate that greater network activation and, specifically, influence of DMN on SAL, support negativity bias among previously depressed individuals.


Effects of Zero-time Exercise on inactive adults with insomnia disorder: a pilot randomized controlled trial.
To evaluate the feasibility and clinical effects of a lifestyle-integrated exercise, namely zero-time exercise (ZTEx), on improving insomnia in inactive adults with insomnia disorder. In this pilot randomized controlled trial, 37 physically inactive adults (mean age: 49.9 years; SD: 13.6 91.9% female) fulfilling the diagnostic criteria of insomnia disorder recruited from the community were randomly assigned to ZTEx training or sleep hygiene education (SHE) groups. Subjects in the ZTEx group (n = 18) attended two 2-hour training lessons to learn ZTEx which they then practiced daily for eight weeks. Subjects in the SHE group (n = 19) attended two lessons of the same schedule and duration. The primary outcome measure was the Insomnia Severity Index (ISI). The ZTEx group had lower ISI scores than the SHE group, with a large between-group effect size of 0.93-1.10 at weeks two, four, six, and eight, but the difference became non-significant at week eight, suggesting a loss of efficacy two months after the training. For secondary outcomes, no significant between-group differences were found in sleep parameters by sleep diary or objective actigraphy. The adherence to the ZTEx training course was satisfactory, with 83% of the group completing two sessions and 78% continuing to practice ZTEx for five days or more per week during the eight-week intervention period. The simple and brief ZTEx training showed high acceptability and exercise compliance and the first evidence of efficacy in reducing insomnia severity in inactive adults with insomnia disorder. Confirmatory trials with longer follow-up are justified. ClinicalTrials.gov, #NCT03155750.


Demographic risk factors for lymphoma in Australian dogs: 6201 cases.
Lymphoma is common in the dog. Studies of population risk factors primarily have been derived from referral institution or insurance data. To identify and quantify the host risk factors for lymphoma in a broad population of Australian dogs. Data on 6201 client owned dogs were retrieved from a commercial veterinary laboratory, a general practice group and 2 referral hospitals. Data collected included breed, sex, and neuter status. A reference population of 640 105 dogs was generated from the referral hospitals and from council registration data. The risk of lymphoma by sex and neuter status was calculated as odds ratios (OR). The study identified 30 breeds at increased risk of lymphoma, 15 that have not been reported previously, and 26 breeds at decreased risk, 18 that have not been reported previously. Males were over represented compared to females with an OR of 1.1 (95% CI, 1.1-1.2; P < .001). Neutered animals were at higher risk compared to intact animals with an OR of 3.2 (95% CI, 2.9-3.5) which was found in both males (OR, 2.8; 95% CI; 2.5-3.2) and females (OR, 4.4; 95% CI, 3.5-5.1). Breed, sex, and neuter status alter the risk of lymphoma in dogs. These 3 factors must be considered when evaluating lymphoma risk as potential markers of underlying differences in disease etiology. Comparison of breeds at increased and decreased risk could be advantageous when evaluating specific etiological factors.


Why Physicians Should Advocate for Undocumented Immigrants' Unimpeded Access to Prenatal Care.
Nearly 7% of US citizens born each year have at least one undocumented parent, but many pregnant undocumented immigrants are ineligible for public insurance covering prenatal care due to their immigration status. This article reviews national-level and state-level policies affecting access to prenatal care for members of this population. This article also considers ethical challenges posed by some policies that create obstacles to patients' accessing health care that is universally recommended by professional guidelines.


Effect of Food on the Pharmacokinetics and Pharmacodynamics of a Novel Dual Delayed-Release Formulation of Esomeprazole in Healthy Subjects.
A novel dual delayed-release formulation (DR) of esomeprazole was developed to prolong the effect of esomeprazole inhibiting gastric acid secretion. This study investigated the effect of food on the pharmacokinetics (PK) and pharmacodynamics (PD) of DR esomeprazole. A randomized, open-label, single-dose, 2-period, 2-sequence crossover study was conducted in healthy Korean subjects. Subjects were orally administered a single dose of 40- mg DR esomeprazole in fasted and fed states in each period. PK and PD characteristics evaluated through continuous 24-hour intragastric pH monitoring in fasted and fed states were compared between the 2 conditions. A total of 23 subjects completed the study and were included in the PK analysis. PD analysis was conducted in 21 subjects, excluding 2 subjects, because of inappropriate pH profiles. The systemic exposure of esomeprazole after a single dose of DR esomeprazole in the fed state decreased compared to that in the fasted state. However, the percentage decrease from baseline in integrated gastric acidity and the percentage of time at pH ≥4 were not significantly different between the 2 conditions. In conclusion, although the systemic exposure of esomeprazole decreased when DR esomeprazole was administered in the fed state compared to that in the fasted state, the degree of gastric acid secretion inhibition was not clinically different, regardless of food intake.


Social Support and Job Satisfaction in Kindergarten Teachers: The Mediating Role of Coping Styles.
This study explored the relationship between social support and job satisfaction in kindergarten teachers, and the mediating role of coping styles in this relationship. A sample of 617 kindergarten teachers (M age = 25.13 years, SD = 5.66 years) from kindergartens in mainland China completed questionnaires measuring social support, job satisfaction, and coping style. The results showed that social support was positively related to job satisfaction and positive coping style was positively associated with social support and job satisfaction. Furthermore, the results revealed that positive coping style, but not negative coping style, had a mediating effect on the relationship between kindergarten teachers' social support and job satisfaction. This study provides initial evidence that coping style mediates the link between social support and job satisfaction in kindergarten teachers, and suggests that increasing social support and encouraging positive coping style could improve kindergarten teachers' job satisfaction.


Intra-alveolar surgical uprighting of impacted teeth: a case report.
Although orthodontic repositioning of impacted teeth is widely used, the treatment has its limitations. Autotransplantation or intra-alveolar surgical repositioning of teeth is an alternative therapy that may be used in selected cases of desperate impactions, when orthodontic extrusion is unsuccessful or when orthodontic treatment is rejected by the patient. A case report is presented to stress both the indications and limitations of a modified technique of intra-alveolar surgical uprighting of impacted teeth.


Beyond refractory obsessions and anxiety states: toward remission.
At the Sixth International Obsessive-Compulsive Disorder Conference (IOCDC), held November 13-15, 2003, in Lanzarote, Spain, 2 issues were discussed that are of great importance to future research on obsessive-compulsive disorder (OCD). The first of these is the possible inclusion of obsessive-compulsive spectrum disorders (OCSD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. OCSD resemble OCD in their clinical symptoms, associated features, comorbidity, family/genetics, etiology, and neurocircuitry, as well as their selective response to treatment with serotonin reuptake inhibitors. The second issue is considering remission as the ultimate goal of treatment for OCD instead of just symptom reduction, as has been suggested in other disorders. These and other issues should be discussed at future meetings of the IOCDC and influence how we conceptualize the disorder and design future treatment trials.


A comparison of least squares regression and geographically weighted regression modeling of West Nile virus risk based on environmental parameters.
The primary aim of the study reported here was to determine the effectiveness of utilizing local spatial variations in environmental data to uncover the statistical relationships between West Nile Virus (WNV) risk and environmental factors. Because least squares regression methods do not account for spatial autocorrelation and non-stationarity of the type of spatial data analyzed for studies that explore the relationship between WNV and environmental determinants, we hypothesized that a geographically weighted regression model would help us better understand how environmental factors are related to WNV risk patterns without the confounding effects of spatial non-stationarity. We examined commonly mapped environmental factors using both ordinary least squares regression (LSR) and geographically weighted regression (GWR). Both types of models were applied to examine the relationship between WNV-infected dead bird counts and various environmental factors for those locations. The goal was to determine which approach yielded a better predictive model. LSR efforts lead to identifying three environmental variables that were statistically significantly related to WNV infected dead birds (adjusted R2 = 0.61): stream density, road density, and land surface temperature. GWR efforts increased the explanatory value of these three environmental variables with better spatial precision (adjusted R2 = 0.71). The spatial granularity resulting from the geographically weighted approach provides a better understanding of how environmental spatial heterogeneity is related to WNV risk as implied by WNV infected dead birds, which should allow improved planning of public health management strategies.


[Effects of spatial-imagery task performance on the heart rate variability].
Effects of the efficiency of spatial task performance on the autonomic heart control were studied. Dynamic changes in autonomic balance diagnosed on the heart rate variability during maze-model task performance (the type of spatial-imagery activity) showed that the type of heart rate regulation depended on the performance efficiency. The results suggest that in subjects with low performance efficiency, problems in performance are associated with negative emotions that produce the emotional psychogenic stress. In subjects with high efficiency, the autonomic contour of the heart rate regulation prevailed. This was presumable associated with the adequacy of the maze-model task.


Immediate care of cardiac emergencies.
The emergency treatment of serious disorders of cardiac rhythm, left heart failure, cardiogenic shock, and cyanotic attacks is discussed. The article is intended for medical practitioners without special cardiological experience.


Improving the Quality of Nasal Specimen Collection for Influenza A and B Screening.
PROBLEM: Rapid diagnosis of seasonal influenza leads to optimized clinical care and reduces the spread of infection. The collection of adequate cellular material can be facilitated by the presence of moisture in the nares. The specific aim of this project was to determine if the installation of sterile saline into the nares prior to specimen collection would improve the quality of the specimen. This quasi-experimental single group design tested an initial "dry swab" specimen against a second swab after instillation of sterile saline solution using a nasal atomizer, a "wet swab." A total of 80 paired specimens were collected and analyzed between December 7, 2015, and April 21, 2016, with an 11.25% infection rate in those tested. Of 9 positive tests, 6 subjects tested positive for influenza A or B for both the dry swab and the wet swab. Three subjects tested positive for influenza A or B for only the wet swab, and these subjects had experienced their symptoms longer than did subjects who tested positive for both methods (mean symptom onset of 72 hours vs 66 hours). We found an important inconsistency between manufacturers' recommendations and typical hospital practice. The results appear somewhat equivocal. Because viral shedding declines after the first 48 to 72 hours in adults, the wet swab method may be clinically superior for detecting influenza in adults presenting later in the course of their illness. Hospital policy was revised for consistency in using the gel medium before sampling in accordance with manufacturer recommendations.


Role of larval sexual dimorphism, biased sex ratios, and habitat on the energetics of a tropical chironomid.
Larval sex dimorphism, fecundity, and sex ratios have been rarely studied in lotic insects, but can have ecological, energetic, and evolutionary importance. I evaluated the effect of microhabitat quality on larval and pupal sex dimorphism and sex ratios using a Hawaiian chironomid (Telmatogeton torrenticola Terry) and examined differences between sex-corrected and noncorrected biomass and secondary production estimates. Larvae and pupae were collected from two microhabitat types defined by microscale flow hydraulics to test for habitat effects on sex dimorphism, sex ratios, fecundity, standing stock biomass, secondary production, and Production/Biomass (P/B) ratios. Female larvae were more than twice as large as males, and this was more pronounced in pupae. Males were twice as abundant as females, and there was no effect of habitat on fourth-instar density. There was, however, a significant habitat effect on morphology, larval body size, standing stock biomass, secondary production, and P/B ratios. Biomass was not statistically different between sexes, but sex-corrected biomass was significantly lower than noncorrected biomass in both habitats but is likely not biologically significant. Sex-corrected secondary production estimates were 69-85% of noncorrected estimates depending on habitat, and sex correction did have a significant effect on P/B ratios in microhabitats of lower quality. This study is one of the first to address sex dimorphism and sex ratios in estimates of standing stock biomass and secondary production, providing initial evidence that microhabitat quality is important to understanding chironomid population biology and the potential role of sex-related demographics in estimates of productivity.


Current readings: Aortic valve-sparing operations.
It has been more than 2 decades since aortic valve-sparing operations were introduced to preserve the aortic valve in patients with aortic root aneurysm. Remodeling of the aortic root is physiologically superior to reimplantation of the aortic valve, mostly because it preserves the aortic annulus movement during the cardiac cycle. However, several comparative studies have shown that reimplantation of the aortic valve has provided more stable aortic valve function than remodeling of the aortic root. This difference in outcomes is largely because of patients׳ selection. Remodeling of the aortic root has been associated with high failure rates in patients with aneurysms associated with genetic syndromes and bicuspid aortic valves with dilated aortic annulus, but it has provided excellent long-term results in older patients with aortic root aneurysms secondary to ascending aortic aneurysms and normal aortic annulus. Thus, both techniques are useful in preserving the aortic valve. With either technique, restoration of normal aortic annulus and cusp geometry is the single most important technical aspect of these operations. In addition to having a competent valve with no or trivial aortic insufficiency at the end of the operation, there must be no cusp prolapse and the coaptation level of the cusps has to be well above the level of the nadir of the aortic annulus.


Demonstration of charge breeding in a compact room temperature electron beam ion trap.
For the first time, a small room-temperature electron beam ion trap (EBIT), operated with permanent magnets, was successfully used for charge breeding experiments. The relatively low magnetic field of this EBIT does not contribute to the capture of the ions; single-charged ions are only caught by the space charge potential of the electron beam. An over-barrier injection method was used to fill the EBIT's electrostatic trap with externally produced, single-charged potassium ions. Charge states as high as K(19+) were reached after about a 3 s breeding time. The capture and breeding efficiencies up to 0.016(4)% for K(17+) have been measured.


Effectiveness of Quiz-Enhanced Videocasts for the Review of Foundational Sciences in the Podiatry Curriculum.
Integrated medical curricula commonly require the review of foundational science concepts in the context of clinical applications. A detailed analysis of the Des Moines University second-year medical curricula revealed that such reviews, conducted as hours-long basic science lectures in second-year clinical systems courses, often create undesirable redundancy and can load the curriculum with excessively detailed content. We hypothesized that short, quiz-enhanced videocasts (QEVs) would allow a more focused and efficient review of foundational sciences than traditional lectures. Five biochemistry lectures in the second year Des Moines University Doctor of Podiatric Medicine curriculum were reviewed for relevance and redundancy, shortened to 8- to 12-min QEVs and offered to students as an alternative to the respective hours-long lecture. Download data show that students chose content delivery by QEV as frequently as delivery of lectures, with QEV use peaking in the days immediately preceding the exam. Survey comments show that students appreciate the efficiency and flexibility of content delivery by QEV, particularly for focused exam preparation. We conclude that the review of foundational concepts by means of short, interactive videocasts can reduce redundant and excessively detailed content from integrated curricula. Although the faculty effort for context review, content selection, and videocast production is higher than for the design of a traditional lecture, the end product offers students a much-appreciated opportunity for efficient, focused, and individualized learning.


A comparison of the effects of plasma exchange and immunoadsorption on anti-insulin antibody synthesis in rabbits.
Plasma exchange (PE) and ex vivo immunoadsorption (IA) may be applicable to the removal of anti-insulin antibodies (AI-Ab) from diabetic patients. However, the removal of antibodies may prompt an increase in their rate of synthesis and an overshoot of antibody levels which may be deleterious to the patient. The effects of both PE and IA on AI-Ab synthesis were studied in a rabbit model. Rabbits were immunized with insulin and the resulting AI-Abs removed by both plasma exchange and specific immunoadsorption. Following AI-Ab removal by PE no increase in AI-Ab synthesis or antibody overshoot occurred. However a large increase in AI-Ab synthesis and overshoot occurred following specific AI-Ab removal by immunoadsorption. Despite similar reductions in AI-Ab levels by PE and IA, no increase in antibody synthesis occurred due solely to antibody removal. It is likely that antigen released from the immunoadsorbent stimulated the increase in antibody synthesis following immunoadsorption. These findings are relevant to the clinical application of both PE and IA.


Association of the fatty acid composition of serum phospholipids with hemostatic factors.
It has been suggested that the fatty acid composition of serum phospholipids is an independent risk factor for cardiovascular disease. We examined the association of the fatty acid composition of serum phospholipids with fibrinogen, factor VII antigen (FVII:Ag), factor VII coagulant activity (FVII:C), plasminogen, and lipoprotein(a) [Lp(a)] in 338 men and 363 women 45 to 64 years old. Palmitic acid, the most abundant saturated fatty acid, was positively associated in univariate analyses with plasminogen, which explained 5.2% of its variance among men (P<.0001) and 5.8% among women (P<.0001). Linoleic acid, which is the most abundant polyunsaturated fatty acid, was negatively associated with plasminogen and fibrinogen. This explained 1.1% of the variance in fibrinogen among men (P=.04) and 3.2% among women (P=.0006) and 4.1% of the variance in plasminogen in both sexes (P<.0001). Dihomogammalinolenic acid was positively associated with FVII:Ag and explained 3.7% of its variance among men (P=.0003) and 4.6% among women (P<.0001). Furthermore, dihomogammalinolenic acid was positively and significantly associated with FVII:C, fibrinogen, and plasminogen among women but not among men. All these associations remained significant after adjustment for multiple potential confounding factors such as age, smoking, serum lipids, and body mass index. In conclusion, our findings suggest that linoleic acid, palmitic acid, and dihomogammalinoleic acid are significant independent determinants of hemostatic profile. It is not clear, however, to what extent these results reflect the effects of fatty acids on coagulation and to what extent they reflect the activity of inflammatory processes in the arteries.


Interleukin-13 inhibits protein kinase C-triggered respiratory burst in human monocytes. Role of calcium and cyclic AMP.
Interleukin-13 (IL-13), a novel cytokine produced by activated lymphocytes modulates some monocyte functions, but no data is available concerning the signal transduction pathway. We show here, the inhibitory effect of IL-13 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-triggered reactive oxygen intermediate production in human monocytes and the signals involved in this response. Our results show that IL-13 produces rapid and transient phosphoinositide hydrolysis and intracellular Ca2+ mobilization. Furthermore, IL-13 induces intracellular cAMP accumulation through inositol 1,4,5-trisphosphate-dependent Ca2+ mobilization. Metabolic inhibitors were used to relate the first steps in signaling pathways to the inhibitory effect of IL-13 on TPA-triggered reactive oxygen intermediate production. Indeed, inhibitors of phospholipase C (neomycin), intracellular Ca2+ mobilization (8-[N,N-diethylamino]-octyl 3,4,5-trimethoxybenzoate hydrochloride), adenylate cyclase (delta 9-tetrahydrocannabinol), and protein kinase A (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) impair the IL-13 inhibitory response. Altogether these observations indicate that modulatory effect of IL-13 on the TPA-induced oxidative burst is the result of the intracellular cAMP accumulation through an inositol 1,4,5-trisphosphate-induced Ca2+ mobilization-dependent pathway.


Redistribution of crossed cerebellar diaschisis.
Crossed cerebellar diaschisis refers to a functional decrease in blood flow to the cerebellar hemisphere contralateral to the infarcted or ischemic cerebral hemisphere. This phenomenon can be depicted using PET as well as using SPECT. This condition, seen on early I-123 IMP brain scans, can show redistribution on the three hour delayed scan, presumably due to normal non-specific amine receptor sites of the affected cerebellum. One such case is reported.


Evolution and divergence of SBP-box genes in land plants.
Squamosa promoter binding protein (SBP)-box family genes encode plant-specific transcription factors that control many important biological functions, including phase transition, inflorescence branching, fruit ripening, and copper homeostasis. Nevertheless, the evolutionary patterns of SBP-box genes and evolutionary forces driving them are still not well understood. 104 SBP-box gene candidates of five representative land plants were obtained from Phytozome database (v10.3). Phylogenetic combined with gene structure analyses were used to identify SBP-box gene lineages in land plants. Gene copy number and the sequence and structure features were then compared among these different SBP-box lineages. Selection analysis, relative rate tests and expression divergence were finally used to interpret the evolutionary relationships and divergence of SBP-box genes in land plants. We investigated 104 SBP-box genes from moss, Arabidopsis, poplar, rice, and maize. These genes are divided into group I and II, and the latter is further divided into two subgroups (subgroup II-1 and II-2) based on phylogenetic analysis. Interestingly, subgroup II-1 genes have similar sequence and structural features to group I genes, whereas subgroup II-2 genes exhibit intrinsic differences on these features, including high copy numbers and the presence of miR156/miR529 regulation. Further analyses indicate that subgroup II-1 genes are constrained by stronger purifying selection and evolve at a lower substitution rate than II-2 genes, just as group I genes do when compared to II genes. Among subgroup II-2 genes, miR156 targets evolve more rapidly than miR529 targets and experience comparatively relaxed purifying selection. These results suggest that group I and subgroup II-1 genes under strong selective constraint are conserved. By contrast, subgroup II-2 genes evolve under relaxed purifying selection and have diversified through gene copy duplications and changes in miR156/529 regulation, which might contribute to morphological diversifications of land plants. Our results indicate that different evolutionary rates and selection strengths lead to differing evolutionary patterns in SBP-box genes in land plants, providing a guide for future functional diversity analyses of these genes.


Ulva lactuca polysaccharides prevent Wistar rat breast carcinogenesis through the augmentation of apoptosis, enhancement of antioxidant defense system, and suppression of inflammation.
Recently, several research studies have been focused on the isolation and function of the polysaccharides derived from different algal species, which revealed multiple biological activities such as antioxidant and antitumor activities. This study assesses the possible breast cancer chemopreventive properties of common seaweeds, sea lettuce, Ulva lactuca (ulvan) polysaccharides using in vitro bioassays on human breast cancer cell line (MCF-7) and an in vivo animal model of breast carcinogenesis. Cytotoxic effect of ulvan polysaccharides on MCF-7 was tested in vitro. For an in vivo investigation, a single dose of 25 mg/kg body weight 7,12-dimethylbenz[a]anthracene (DMBA) and ulvan polysaccharides (50 mg/kg body weight every other day) for 10 weeks were administered orally to the Wistar rats. Deleterious histopathological alterations in breast tissues including papillary cyst adenoma and hyperplasia of ductal epithelial lining with intraluminal necrotic materials and calcifications were observed in the DMBA-administered group. These lesions were prevented in the DMBA-administered group treated with ulvan polysaccharides. The immunohistochemical sections depicted that the treatment of DMBA-administered rats with ulvan polysaccharides markedly increased the lowered pro-apoptotic protein, p53, and decreased the elevated anti-apoptotic marker, bcl2, expression in the breast tissue. The elevated lipid peroxidation and the suppressed antioxidant enzyme activities in DMBA-administered control were significantly prevented by the treatment with ulvan polysaccharides. The elevated levels of inflammatory cytokines tumor necrosis factor-α and nitric oxide were significantly ameliorated in DMBA-administered rats treated with ulvan polysaccharides as compared to DMBA-administered control. In conclusion, ulvan polysaccharides at the level of initiation and promotion might have potential chemopreventive effects against breast carcinogenesis. These preventive effects may be mediated through the augmentation of apoptosis, suppression of oxidative stress and inflammation, and enhancement of antioxidant defense system.


Specific and relative detection of urinary microRNA signatures in bladder cancer for point-of-care diagnostics.
We present a dual-isothermal cascade strategy assisted by a lateral flow peptide nucleic acid biosensor for point-of-care detection of urinary microRNAs without a temperature protocol and complex instruments. The proposed assay is expected to be of great promise for bladder cancer diagnosis and point-of-care diagnostics.


Nickel Particles Selectively Confined in the Mesoporous Channels of SBA-15 Yielding a Very Stable Catalyst for DRM Reaction.
A series of four Ni catalysts supported on SBA-15 and on a high SiO2 surface area have been prepared by modified impregnation (ImU) and deposition-precipitation (DP) methods. The catalysts have been extensively characterized, including in situ XAS (bulk sensitive) and XPS (surface sensitive) techniques, and their catalytic activities evaluated in the dry reforming reaction of methane (DRM). The combined use of XPS and XAS has allowed us to determine the location of nickel particles on each catalyst after reduction at high temperature (750 °C). Both Ni/SiO2-DP and Ni/SBA-15-DP catalysts yield well-dispersed and homogeneous metallic phases mainly located in the mesoporosity of both supports. On the contrary, the Ni/SiO2-ImU and Ni/SBA-15-ImU catalysts present a bimodal distribution of the reduced nickel phase, with nickel metallic particles located out and into the mesoporous structure of SiO2 or the SBA-15 channels. The Ni/SBA-15-DP catalyst was found the most stable and performing system, with a very low level of carbon deposition, about an order of magnitude lower than the equivalent ImU catalyst. This outstanding performance comes from the confinement of small and homogeneous nickel particles in the mesoporous channels of SBA-15, which, in strong interaction with the support, are resistant to sintering and coke deposition during the demanding reaction conditions of DRM.


Immunochemical characterization of wild-type and variant glucocorticoid receptors by monoclonal antibodies.
Monoclonal antibodies raised against the rat liver glucocorticoid receptor were used to investigate receptors of wild-type and glucocorticoid-resistant variants of mouse lymphoma cells. Two of the variant types contained receptors of 'nuclear transfer deficient' (nt-) and 'increased nuclear transfer' (nti) phenotypes, respectively, while the third was of the 'receptorless' (r-) phenotype with negligible hormone binding activity. Three monoclonal antibodies of the IgM class and one of the IgG class reacted with both wild-type and nt- receptors but not with the steroid binding form of nti receptors. Some of the antibodies bound the wild-type and nt- receptors more efficiently after activation at 20 degrees C. By use of an immuno-competition assay we were able to detect cross-reacting material in considerable amounts in extracts of nti and r- cell variants. This material was further characterized by gel filtration and immunoblotting. The immunoreactive material of wild-type, nti and r- cells gave a major band of mol. wt. 94 000 upon SDS-gel electrophoresis while the steroid-binding polypeptides of wild-type and nti receptors have mol. wts. of 94 000 and 40 000, respectively. The data show that in S49.1 mouse lymphoma cells the products of two receptor alleles can be distinguished.


Virtual Partnership Addressing Mental Health Crises: Mixed Methods Study of a Coresponder Program in Rural Law Enforcement.
A mental health crisis can create challenges for individuals, families, and communities. This multifaceted issue often involves different professionals from law enforcement and health care systems, which may lead to siloed and suboptimal care. The virtual crisis care (VCC) program was developed to provide rural law enforcement with access to behavioral health professionals and facilitated collaborative care via telehealth technology. This study was designed to evaluate the implementation and use of a VCC program from a telehealth hub for law enforcement in rural areas. This study used a mixed methods approach. The quantitative data came from the telehealth hub's electronic record system. The qualitative data came from in-depth interviews with law enforcement in the 18 counties that adopted the VCC program. Across the 181 VCC encounters, the telehealth hub's recommended disposition and the actual disposition were similar for remaining in place (n=141, 77.9%, and n=137, 75.7%, respectively), voluntary admission (n=9, 5.0%, and n=10, 5.5%, respectively), and involuntary committal (IVC; n=27, 14.9%, and n=19, 10.5%, respectively). Qualitative insights related to the VCC program's implementation, use, benefits, and challenges were identified, providing a comprehensive view of the virtual partnership between rural law enforcement and behavioral health professionals. Use of a VCC program likely averts unnecessary IVCs. Law enforcement interviews affirmed the positive impact of VCC due to its ease of use and the benefits it provides to the individuals in need, the first responders involved, law enforcement resources, and the community.


Quantitative trait loci and genes associated with salmonid alphavirus load in Atlantic salmon: implications for pancreas disease resistance and tolerance.
Salmonid alphavirus infection results in pancreas disease causing severe economic losses for Atlantic salmon aquaculture. Knowledge about genes and pathways contributing to resistance is limited. A 54 K SNP panel was used to genotype 10 full-sibling families each consisting of ~ 110 offspring challenged with salmonid alphavirus subtype 3. Relative heart viral load was assessed at 4- and 10-weeks post-infection using quantitative PCR. A moderate genomic heritability of viral load at 4 weeks (0.15-0.21) and a high positive correlation with survival (0.91-0.98) were detected. Positions of QTL detected on chromosome 3 matched those for survival detected by other studies. The SNP of highest significance occurred in the 3' untranslated region of gig1, a fish-specific antiviral effector. Locus B of immunoglobulin heavy chain mapped to an area containing multiple SNPs with genome-wide association. Heart mRNA-seq comparing parr from families with high- versus low-genomic breeding value, and matching sample genotypes for SNPs, identified two eQTL for salmonid alphavirus load. Immune genes associated with trans-eQTL were numerous and spread throughout the genome. QTL regions contained several genes with known or predicted immune functions, some differentially expressed. The putative functional genes and variants identified could help improve marker-based selection for pancreas disease resistance.


Doxorubicin and vincristine with methionine depletion contributed to survival in the Yoshida sarcoma bearing rats.
Several anti-cancer agents show increased toxicity if administered with methionine-depleting total parenteral nutrition (Met-deplete TPN). Changes in the cell cycle due to Met-deplete TPN were investigated, and then the enhancement of the anti-tumor effects of serial combinations of doxorubicin (ADM), a drug acting on late S-G2 phase and vincristine (VCR), an antimitotic drug, under Met-deplete TPN was also examined in the tumor-bearing rats. According to the fraction of labeled mitosis, within 3 to 4 days after the introduction of Met-deplete TPN in the ascites type Yoshida sarcoma (YS) -bearing rats, the cell cycle of the tumor cells showed marked delay and the fraction of labeled mitosis decreased to less than 70%. However, this delay was recovered immediately after methionine infusion, with on increase in the labeled mitotic cell population. In the experiment using solid type YS-bearing rats, ADM was administered intraperitoneally under Met-deplete TPN for 8 days, followed by intraperitoneal VCR administration with methionine-containing TPN for 3 days, and then fed on solid food and water ad libitum until death. This serial combination of Met-deplete TPN with ADM and VCR resulted in marked suppression of the tumor and prolonged survival in comparison to the control groups with a significant difference (p < 0.001) (generalized Wilcoxon test).


Differential effects of fibroblast growth factors on expression of genes of the plasminogen activator and insulin-like growth factor systems by human breast fibroblasts.
In breast stroma urokinase plasminogen activator (uPA) is predominantly expressed by fibroblasts located in the near vicinity of tumor cells, and fibroblast-derived insulin-like growth factor-1 (IGF-1) may be involved in inhibiting the expression of uPA in these fibroblasts. To investigate a possible role for fibroblast growth factors (FGFs), we evaluated the expression of components of the PA system and the IGF system in normal and tumor-tissue-derived human breast fibroblasts exposed to various FGFs in vitro. mRNA analysis revealed that FGF-1, FGF-2 and FGF-4 induced the mRNA expression levels of uPA, tPA, uPAR, PAI-1 and PAI-2, and reduced those of IGF-1, IGF-1R, IGF-2R and IGFBP-4, without significantly affecting the levels of IGFBP-3, IGFBP-5 and IGFBP-6 mRNA. Concerning the expression of IGF-2 mRNA, the effects mediated by FGF-1, FGF-2 and FGF-4 were divergent. In general, the effects elicited by FGF-1 on the various mRNA levels studied were rapid and short-term. Those mediated by FGF-2 overall lagged behind but were longer-lasting. For FGF-4 an in between pattern was observed. Blocking transcription and translation demonstrated that a) both the FGF-1 and FGF-2 induced effects were the result of altered gene transcription or mRNA stability, b) the short-term effects mediated by FGF-1 and FGF-2 required de novo protein synthesis, and c) the long-term effects elicited by FGF-2 did not depend on de novo protein synthesis during the first 24 h, but were triggered by proteins produced or made available thereafter. The data presented propose that of the FGFs studied (FGF-1, -2, -4, -5, and -7), FGF-2 is the most attractive target for therapeutical strategies aimed at diminishing the contribution of stromal fibroblasts in the PA-directed breast tumor proteolysis.


COVID-19 drug repurposing: Summary statistics on current clinical trials and promising untested candidates.
Repurposing of existing anti-viral drugs, immunological modulators and supportive therapies represents a promising path towards rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A comprehensive text-mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials and previous efforts to develop therapies against related betacoronaviruses, particularly SARS and MERS. In contrast to drugs in current trials, which have been derived overwhelmingly from studies on taxonomically unrelated RNA viruses, a number of untested small molecule anti-virals had previously demonstrated remarkable in vitro specificity for SARS-CoV or MERS-CoV, with high selectivity indices, EC50 and/or IC50 . Due to the rapid containment of the prior epidemics, however, these were generally not followed up with in vivo animal studies or clinical investigations and thus largely overlooked as treatment prospects in the current COVID-19 trials. This brief review summarizes and tabulates core information on recent or ongoing drug repurposing-focused clinical trials, while detailing the most promising untested candidates with prior documented success against the aetiologic agents of SARS and/or MERS.